1536P - Description and prognostic value of the mutational load across various metastatic solid tumors in the prospective MOSCATO-01 and MATCH-R trials

Date 10 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Translational Research
Presenter Linda Mahjoubi
Citation Annals of Oncology (2016) 27 (6): 526-544. 10.1093/annonc/mdw392
Authors L. Mahjoubi1, M. Pedredo2, C. Massard1, E. Castanon Alvarez1, C. Lefebvre2, L. Lacroix3, Y. Loriot4, F. André4, J. Soria1
  • 1Drug Development Department (ditep), Institut Gustave Roussy, 94800 - Villejuif/FR
  • 2Plateforme De Génomique Fonctionnelle, Gustave Roussy, Institut Gustave Roussy, 94800 - Villejuif/FR
  • 3Laboratoire De Recherche Translationnelle Et Centre De Ressources Biologiques, Institut Gustave Roussy, 94800 - Villejuif/FR
  • 4Medical Oncology Department, Institut Gustave Roussy, 94800 - Villejuif/FR

Abstract

Background

MOSCATO-01 and MATCH-R are ongoing prospective precision medicine trials (NCT01566019 and NCT02517892). They allow genomic analysis of purposefully acquired tumor biopsies obtained in patients with various types of metastatic solid tumors. MATCH-R encompassed whole exome sequencing (WES) since its inception, while MOSCATO incorporated WES in 2015.

Methods

To describe the landscape and evaluate the prognostic impact of the mutational load in metastatic solid tumors blinded from histology and history of previous treatment, whole exome sequencing was performed on prospective samples with both high tumor cellularity (> 30%) and good DNA.

Results

Mutational load from 160 patients was obtained, with 9 patients having multiple longitudinal mutational loads and 4 patients with synchronous mutational loads from different biopsies sites. Mutational load was ranging from 0.2 to 28.7 mut/Mb with 80% of patients under 5 mut/Mb. In this heterogeneous population with various preceding therapies, mutational load was not associated with overall survival. Overall survival (OS) trended to be longer in patients with mutational load under 5 mut/Mb (median 18 months [95% CI n.a.] vs 12 months [95% CI 7.1-16.9], p = 0.13). Variations of mutational load highlight importance of histology and history of treatment.

Conclusions

Prospective evaluation of the mutational load is routinely feasible in precision medicine trials. Results were obtained within 4 weeks of tumor biopsy. In this heterogeneous population, mutational load is not prognostic. Signatures of mutational processes and neoantigens are currently being characterized in our patients.

Clinical trial identification

Legal entity responsible for the study

N/A

Funding

N/A

Disclosure

All authors have declared no conflicts of interest.